Bleomycin A5 suppresses Drp1‑mediated mitochondrial fission and induces apoptosis in human nasal polyp‑derived fibroblasts

博来霉素 A5 抑制 Drp1 介导的线粒体裂变并诱导人鼻息肉衍生成纤维细胞凋亡

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作者:Fan Wu #, Yun Ma #, Jingyi Wang, Huashuang Ou, Hua Dang, Yiqing Zheng, Peng Tian, Hua Zou

Abstract

Intralesional injection of bleomycin‑A5 (BLE‑A5) is a novel treatment for nasal polyps. Our previous study clarified that BLE‑A5 could induce nasal polyp‑derived fibroblast (NPDF) apoptosis in nasal polyps. However, the detailed mechanisms are still unclear. The present study aimed to determine the effects of BLE‑A5 on NPDF mitochondrial dynamics and provide a theoretical basis for the local application of BLE‑A5 to treat nasal polyps. In the present study, an in vitro nasal polyp tissue culture model was used to define the BLE‑A5 target cell type in nasal polyps. NPDF primary cell culture was used to study the effects of BLE‑A5 on the mitochondrial dynamic‑related mechanism. The results showed that BLE‑A5 treatment of NPDFs caused mitochondrial‑mediated apoptosis. Dynamin‑related protein 1 (Drp1) was shown to be altered in BLE‑A5‑treated NPDFs. Drp1 knockdown increased the sensitivity of NPDFs to BLE‑A5 and exacerbated mitochondrial dysfunction. BLE‑A5 decreased cyclin B1‑CDK1 complex‑mediated phosphorylation of Drp1 and inhibited Drp1‑mediated mitophagy in NPDFs. Overall, the present study concluded that BLE‑A5 mainly induces NPDF apoptosis in nasal polyps. BLE‑A5 regulates the mitochondria by inhibiting Drp1 activation, resulting in NPDF mitochondrial dynamic disorder and apoptosis.

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